The 1986 explosion at the Chernobyl nuclear power plant released radioactive particles in every direction.

The 1986 Chernobyl nuclear power plant disaster was the worst nuclear accident in history. An explosion at the plant, in what is now Ukraine, released radioactive particles hundreds of miles in every direction.

Now, more than a quarter-century later, the study of some victims exposed to ionizing radiation from that accident is yielding new information about how radiation-induced thyroid cancer develops. It is estimated that more than 6,000 cases of thyroidcancer were caused by the disaster.

“The Chernobyl accident is a clear example of the health consequences experienced by a large population exposed to radioactive iodine,” says Memorial Sloan Kettering physician-scientist James A. Fagin. “The people who were exposed, especially those who were children at the time, have been monitored very closely, and there’s been a lot of interest to see what happens to their risk of cancer over time.”

Children Were the Most Affected

Most of the people in the study were under the age of ten at the time of the accident and developed thyroid cancer as adolescents or young adults. “There’s no question that the frequency of cancer in this group of people is many times what it would have been in a population not exposed to radiation,” Dr. Fagin says.

When the explosion occurred, radioactive iodine isotopes (unstable atoms that give off radiation) were released into the atmosphere. Those isotopes fell onto the grass, which was then ingested by dairy cattle. They also fell onto other crops and entered the food supply, including the maternal milk for breast-fed infants.

Iodine-131, one of the main isotopes that was released, is not very stable and half of it had decayed after a little more than a week. Therefore, although exposure was high, it lasted for a relatively short period of time.

Characterizing the Genomic Changes

The investigators analyzed the genomic changes in DNA that was taken from the tumors of 26 children and young adults who had thyroid cancer. “Because we know the exact age of all the children at the time of exposure and because they have been studied very closely afterward, we consider this to be a well-curated population of patients,” Dr. Fagin explains.

The investigators found that the tumors contained so-called fusion oncogenes that result when DNA breaks apart, swaps places, and fuses back together. Ionizing radiation is known to cause DNA breaks, which is the mechanism by which radiation induces cancer.

“What’s really remarkable is that in every single one of these cases, we were able to find the driver mutation — the actual genetic change that caused the cancer. “

-James Fagin, physican-scientist

“We found that all of these fusion oncogenes fell into particular functional classes,” he says. “They tend to be activated receptors or activated signaling proteins of pathways that are known to induce cancer. To a large extent, the oncogenes implicated were ones that were already known to play a role in thyroid cancer.

“What’s really remarkable is that in every single one of these cases, we were able to find the driver mutation — the actual genetic change that caused the cancer,” he says. “That’s not very common in most cancer studies, even when you sequence the entire genome of the tumors.

Lessons Learned, but Questions Remain

“The study’s findings reveal two important things,” Dr. Fagin says. “One, that radiation causes a particular type of genetic damage that is associated with characteristic cancer genes; and two, that those genes turn on the activities of pathways that are critical for the formation of thyroid cancer.”

So far there has been no definitive link to Chernobyl exposure and the development of other cancers. “But it’s still early days,” Dr. Fagin concludes. “For thyroid cancer, the latency, or time between exposure and cancer, is shorter than we would have predicted. For other cancers, it’s possible that we could see increases in the future.

This study was supported by the National Institutes of Health under grants CA50706, CA72597, R01HG006798, R01NS076465, and R44HG005297; the Margot Rosenberg Pulitzer Foundation; the Byrne fund; and the Lefkofsky Family Foundation.

analysis (uh-NA-lih-sis)

A process in which anything complex is separated into simple or less complex parts.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

DNA

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

genetic (jeh-NEH-tik)

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

genome (JEE-nome)

The complete genetic material of an organism.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

gland (gland)

An organ that makes one or more substances, such as hormones, digestive juices, sweat, tears, saliva, or milk. Endocrine glands release the substances directly into the bloodstream. Exocrine glands release the substances into a duct or opening to the inside or outside of the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

investigator (in-VES-tih-gay-ter)

A researcher in a clinical trial or clinical study.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

iodine (I-oh-dine)

An element that is necessary for the body to make thyroid hormone. It is found in shellfish and iodized salt.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

ionizing radiation (I-uh-NY-zing RAY-dee-AY-shun)

A type of radiation made (or given off ) by x-ray procedures, radioactive substances, rays that enter the Earth's atmosphere from outer space, and other sources. At high doses, ionizing radiation increases chemical activity inside cells and can lead to health risks, including cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

maternal (muh-TER-nul)

Having to do with the mother, coming from the mother, or related through the mother.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

mutation (myoo-TAY-shun)

Any change in the DNA of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial, or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; if mutations occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

radiation (RAY-dee-AY-shun)

Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

radioactive (RAY-dee-oh-AK-tiv)

Giving off radiation.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

radioactive iodine (RAY-dee-oh-AK-tiv I-oh-dine)

A radioactive form of iodine, often used for imaging tests or to treat an overactive thyroid, thyroid cancer, and certain other cancers. For imaging tests, the patient takes a small dose of radioactive iodine that collects in thyroid cells and certain kinds of tumors and can be detected by a scanner. To treat thyroid cancer, the patient takes a large dose of radioactive iodine, which kills thyroid cells. Radioactive iodine is also used in internal radiation therapy for prostate cancer, intraocular (eye) melanoma, and carcinoid tumors. Radioactive iodine is given by mouth as a liquid or in capsules, by infusion, or sealed in seeds, which are placed in or near the tumor to kill cancer cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

thyroid (THY-royd)

A gland located beneath the larynx (voice box) that makes thyroid hormone and calcitonin. The thyroid helps regulate growth and metabolism. Also called thyroid gland.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

thyroid cancer (THY-royd KAN-ser)

Cancer that forms in the thyroid gland (an organ at the base of the throat that makes hormones that help control heart rate, blood pressure, body temperature, and weight). Four main types of thyroid cancer are papillary, follicular, medullary, and anaplastic thyroid cancer. The four types are based on how the cancer cells look under a microscope.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)